He is using modeling and mathematical and computational analysis to study intercellular communication via ion flow in the brain-cell microenvironment and how restricted diffusion of ions can alter brain function. He says that understanding the brain is “one of the remaining major frontiers in human knowledge.”

“There is an enormous published literature on the detailed mechanisms operative in the brain,” he says. “But our knowledge of how the combination of these mechanisms leads to the functioning mammalian brain remains very incomplete.”

With a grant from the National Science Foundation, he is leading a research team in a study of cortical spreading depression (CSD), a nonlinear chemical and electrical (slow) wave phenomenon in the cortices of different brain structures. These waves are characterized by depression of cellular electrical activity and pathological shifts in ion concentrations. CSD is known to be connected with migraine with aura, and may also have a relationship to other conditions, such as stroke and transient global amnesia. The research team, which includes Professors Huaxiong Huang of York University, Ontario, Canada and Jonathan Wylie of City University of Hong Kong, is working to identify the relevant mechanisms that appear involved in cortical spreading depression and to include them in a comprehensive model of CSD.

The pathological shifts in ion concentrations during CSD has led the research team to look more carefully at the energy sources needed to activate ionic pumps so the system can recover ion homeostasis. This has led them to incorporating blood vessels into their models because the brain vascular system provides the oxygen needed for ATP synthesis for the pumps.

“In spite of knowing many of the basic mechanisms involved in CSD,” Miura said, “we still do not understand the relative importance of these mechanisms and how they conspire to produce the observed wave phenomena. We can greatly extend our basic knowledge of how the brain functions by understanding what happens and causes the ‘massive failure of ion homeostasis’ during CSD. It is extremely difficult to perform detailed experiments that record the multifarious variables that are changing during CSD. Therefore, a good understanding of the complex interactions between these mechanisms can come only from a detailed mathematical modeling viewpoint where one can turn mechanisms on and off.”